Deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase: a cause of lethal myopathy and cardiomyopathy in early childhood.
A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood beta-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the C6 to C10 dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium- and long-chain (C8 to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium- and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacyl-CoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and long-chain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts.
Rocchiccioli
F
F
Unité 188 INSERM, Saint Vincent de Paul Hospital, Paris, France.
Wanders
R J
RJ
Aubourg
P
P
Vianey-Liaud
C
C
Ijlst
L
L
Fabre
M
M
Cartier
N
N
Bougneres
P F
PF
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism; D007223:Infant; D050356:Lipid Metabolism; D008099:Liver / Q000648:ultrastructure; D009132:Muscles / Q000648:ultrastructure; D009135:Muscular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D044942:Acyl-CoA Dehydrogenase, Long-Chain